PMID- 32170673
OWN - NLM
STAT- MEDLINE
DCOM- 20210129
LR  - 20210129
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Print)
IS  - 0364-3190 (Linking)
VI  - 45
IP  - 5
DP  - 2020 May
TI  - The Novel Role of PPAR Alpha in the Brain: Promising Target in Therapy of 
      Alzheimer's Disease and Other Neurodegenerative Disorders.
PG  - 972-988
LID - 10.1007/s11064-020-02993-5 [doi]
AB  - Peroxisome proliferator activated receptor alpha (PPAR-alpha) belongs to the family 
      of ligand-regulated nuclear receptors (PPARs). These receptors after 
      heterodimerization with retinoid X receptor (RXR) bind in promotor of target 
      genes to PPAR response elements (PPREs) and act as a potent transcription 
      factors. PPAR-alpha and other receptors from this family, such as PPAR-beta/delta and PPAR-gamma 
      are expressed in the brain and other organs and play a significant role in 
      oxidative stress, energy homeostasis, mitochondrial fatty acids metabolism and 
      inflammation. PPAR-alpha takes part in regulation of genes coding proteins that are 
      involved in glutamate homeostasis and cholinergic/dopaminergic signaling in the 
      brain. Moreover, PPAR-alpha regulates expression of genes coding enzymes engaged in 
      amyloid precursor protein (APP) metabolism. It activates gene coding of alpha 
      secretase, which is responsible for non-amyloidogenic pathway of APP degradation. 
      It also down regulates beta secretase (BACE-1), the main enzyme responsible for 
      amyloid beta (Abeta) peptide release in Alzheimer Diseases (AD). In AD brain 
      expression of genes of PPAR-alpha and PPAR-gamma coactivator-1 alpha (PGC-1alpha) is 
      significantly decreased. PPARs are altered not only in AD but in other 
      neurodegenerative/neurodevelopmental and psychiatric disorder. PPAR-alpha 
      downregulation may decrease anti-oxidative and anti-inflammatory processes and 
      could be responsible for the alteration of fatty acid transport, lipid metabolism 
      and disturbances of mitochondria function in the brain of AD patients. Specific 
      activators of PPAR-alpha may be important for improvement of brain cells metabolism 
      and cognitive function in neurodegenerative and neurodevelopmental disorders.
FAU - Wojtowicz, Sylwia
AU  - Wojtowicz S
AUID- ORCID: 0000-0001-9582-4042
AD  - Department of Cellular Signaling, Mossakowski Medical Research Centre Polish 
      Academy of Sciences, 5 Pawinskiego st., 02-106, Warsaw, Poland. 
      swojtowicz@imdik.pan.pl.
FAU - Strosznajder, Anna K
AU  - Strosznajder AK
AD  - Faculty of Medicine, Medical University of Bialystok, 1 Kilinskiego st., 15-089, 
      Bialystok, Poland.
FAU - Jezyna, Mieszko
AU  - Jezyna M
AD  - Faculty of Medicine, Medical University of Bialystok, 1 Kilinskiego st., 15-089, 
      Bialystok, Poland.
FAU - Strosznajder, Joanna B
AU  - Strosznajder JB
AD  - Department of Cellular Signaling, Mossakowski Medical Research Centre Polish 
      Academy of Sciences, 5 Pawinskiego st., 02-106, Warsaw, Poland. 
      jstrosznajder@imdik.pan.pl.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200313
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (PPAR alpha)
RN  - U202363UOS (Fenofibrate)
SB  - IM
MH  - Alzheimer Disease/drug therapy/*metabolism
MH  - Animals
MH  - Brain/drug effects/*metabolism
MH  - Drug Delivery Systems/*trends
MH  - Fenofibrate/administration & dosage/metabolism
MH  - Humans
MH  - Neurodegenerative Diseases/drug therapy/metabolism
MH  - PPAR alpha/agonists/*metabolism
PMC - PMC7162839
OTO - NOTNLM
OT  - App/abeta metabolism
OT  - Glutamatergic signaling
OT  - Mitochondria function
OT  - Neurodegeneration
OT  - Neuroprotection
OT  - PPAR-alpha
COIS- All authors have nothing to disclose.
EDAT- 2020/03/15 06:00
MHDA- 2021/01/30 06:00
PMCR- 2020/03/13
CRDT- 2020/03/15 06:00
PHST- 2019/12/08 00:00 [received]
PHST- 2020/02/17 00:00 [accepted]
PHST- 2020/02/11 00:00 [revised]
PHST- 2020/03/15 06:00 [pubmed]
PHST- 2021/01/30 06:00 [medline]
PHST- 2020/03/15 06:00 [entrez]
PHST- 2020/03/13 00:00 [pmc-release]
AID - 10.1007/s11064-020-02993-5 [pii]
AID - 2993 [pii]
AID - 10.1007/s11064-020-02993-5 [doi]
PST - ppublish
SO  - Neurochem Res. 2020 May;45(5):972-988. doi: 10.1007/s11064-020-02993-5. Epub 2020 
      Mar 13.